Immunologic analysis of 156 patients with hereditary angioedema has been completed and it has been shown that about a third have autoimmune manifestations. However, in the vast majority of patients, these manifestations are clinically minor. Analysis of T cell subsets indicate that patients with hereditary angioedema have elevated numbers of helper cells and normal numbers of suppressor cells. The origin of the increase in helper cells is not known but there is a clear correlation between complement activation and helper cell number. Thus, patients with marked disease activity as manifested by complement activation have an increased number of helper cells when compared to patients with minimal activation of complement. In other studies, efforts are underway to further analyze a series of patients with acquired angioedema. A number of these patients have been followed for up to a decade at the National Institutes of Health. These patients tend to have O levels of C4, C2 and no functional C1 esterase inhibitor. Careful analysis of serum suggests that they have a protein bound to the C1 inhibitor and that such protein is an antibody. Another major interest in our laboratory has been the expression of complement receptors on phagocytic cells. We had previously shown that peripheral blood monocytes possess the receptor for the complement fragment C3d. In the past year, we have shown that C3d coated particles can be phagocytosed in the presence of particle-bound IgG and that C3d causes marked augmentation of IgG mediated phagocytosis. At present, the identity of the receptor responsible for the binding of the C3d coated particles is not clear. It does not appear to be the same C3d receptor which exists on lymphocytes and may simply represent combined activity of the C3bi and C3b receptors respectively.